Delayed Heart Rate Recovery Research Articles

Autonomic Dysfunction Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort Study

BackgroundThe burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown. ObjectivesWe evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors. MethodsWe conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression tested associations with impaired cardiorespiratory fitness (peak Vo2 < 80% predicted). ResultsSurvivors (50.7% female) were 9.0 ± 5.8 years at cancer diagnosis and 35.5 ± 8.9 years at evaluation. Prevalence (survivors vs control subjects) of elevated resting heart rate (17.9% vs 7.0%), decreased heart rate reserve (21.7% vs 9.1%), decreased systolic blood pressure response to exercise (25.3% vs 12.6%), and delayed heart rate recovery (24.3% vs 10.6%) was more than 2-fold higher among survivors (P < 0.001 for all). Carboplatin (adjusted OR: 2.50; 95% CI: 1.42-4.40; P = 0.001), chest-directed radiation therapy (adjusted OR: 2.06; 95% CI: 1.52-2.75; P < 0.001), and cranial radiation (adjusted OR: 1.49; 95% CI: 1.08-2.05; P = 0.015) were associated with an increased likelihood of having ≥2 measures of autonomic dysfunction. Survivors with ≥2 measures of autonomic dysfunction were at increased risk for impaired cardiorespiratory fitness (adjusted OR: 2.71; 95% CI: 1.82-4.02; P < 0.001). ConclusionsSurvivors of childhood cancer manifest a higher prevalence of autonomic dysfunction associated with impaired cardiorespiratory fitness.

Abstract MP25: Buprenorphine pharmacotherapy reduces somatic signs of withdrawal in neonates but may not prevent cardiovascular risk in adult offspring with prenatal fentanyl exposure

Long-term effects on the cardiovascular system of offspring exposed to fentanyl in utero are one of the understudied aspects of the opioid crisis. Previously, we have shown that offspring exposed to opioids in utero display exacerbated somatic signs of withdrawal compared to vehicle-exposed offspring. We also showed that prenatal opioid exposure induce long lasting effects increasing blood pressure (BP) in the adult offspring. Buprenorphine (BUP) is one of the most effective FDA-approved standard-of-care therapies used to treat mothers with opioid use disorder and their newborns with neonatal opioid withdrawal syndrome (NOWS). Yet, long-term effects of BUP in the pediatric population is limited. This study aimed to determine the efficacy of BUP in reducing somatic signs of withdrawal in rat neonates and the long-term effects on BP control. Female Sprague-Dawley rat breeders were implanted with a chronic jugular vein catheter and subjected to 2-hr self-administration (SA) sessions of vehicle (VEH, 0.9% NaCl, n=3) or fentanyl (FEN, 2.5 μg/kg/infusion/lever press, n=3). After rats developed dependence, they were paired during proestrus with males for breeding. SA sessions continued until delivery. There were no changes in maternal weight gain and pup weights at birth. At postnatal day 1, a subset of FEN-SA pups was treated with BUP for 5 consecutive days (1 mg/kg, sc). Video recording was performed daily to quantify somatic signs of withdrawal, including body curls, head movements, and spasms. FEN-SA increased withdrawal at postnatal days 1-3. This effect was attenuated in FEN-SA offspring treated with BUP (p&lt;0.05).14-week-old male offspring were implanted with radiotelemetry (n=4 per group). Compared to VEH-SA, FEN-SA offspring showed: 1) increased BP in response to phenylephrine (PE, 40 µg/kg ip), 2) tachycardic response to 1-hour restraint stress followed by impaired BP recovery (p&lt;0.05, respectively), 3) similar acute responses to AngII (30 µg/kg, sc), 4) exacerbated BP and delayed heart rate recovery in response to acute FEN (20 µg/kg, sc, p&lt;0.05), although plasma clearance was similar between groups. BUP treatment in FEN-SA offspring did not influence acute changes in BP or heart rate to different hypertensive stimuli. Taken together our data suggests that an opioid-based therapy effectively reduced somatic signs of withdrawal; however, it does not seem effective in attenuating the acute and chronic BP responses in prenatal fentanyl-exposed offspring.

Heart rate recovery after orthostatic challenge and cardiopulmonary exercise testing in older individuals: prospective multicentre observational cohort study

Impaired vagal function in older individuals, quantified by the 'gold standard' delayed heart rate recovery after maximal exercise (HRRexercise), is an independent predictor of cardiorespiratory capacity and mortality (particularly when HRR ≤12 beats min-1). Heart rate also often declines after orthostatic challenge (HRRorthostatic), but the mechanism remains unclear. We tested whether HRRorthostatic reflects similar vagal autonomic characteristics as HRRexercise. Prospective multicentre cohort study of subjects scheduled for cardiopulmonary exercise testing (CPET) as part of routine care. Before undergoing CPET, heart rate was measured with participants seated for 3 min, before standing for 3 min (HRRorthostatic). HRRexercise 1 min after the end of CPET was recorded. The primary outcome was the correlation between mean heart rate change every 10 s for 1 min after peak heart rate was attained on standing and after exercise for each participant. Secondary outcomes were HRRorthostatic and peak VO2 compared between individuals with HRRexercise <12 beats min-1. A total of 87 participants (mean age: 64 yr [95%CI: 61-66]; 48 (55%) females) completed both tests. Mean heart rate change every 10 s for 1 min after peak heart rate after standing and exercise was significantly correlated (R2=0.81; P<0.0001). HRRorthostatic was unchanged in individuals with HRRexercise ≤12 beats min-1 (n=27), but was lower when HRRexercise >12 beats min-1 (n=60; mean difference: 3 beats min-1 [95% confidence interval 1-5 beats min-1]; P<0.0001). Slower HRRorthostatic was associated with lower peak VO2 (mean difference: 3.7 ml kg-1 min-1 [95% confidence interval 0.7-6.8 ml kg-1 min-1]; P=0.039). Prognostically significant heart rate recovery after exhaustive exercise is characterised by quantitative differences in heart rate recovery after orthostatic challenge. These data suggest that orthostatic challenge is a valid, simple test indicating vagal impairment. researchregistry6550.

Assessment of Cardiovascular Parameters on Submaximal Treadmill Exercise in Obese versus Nonobese Adults.

Obesity and overweight, irrespective of metabolic status, confer an increased risk of adverse consequences including cardiovascular diseases (CVDs). The mechanisms underlying altered cardiovascular responses in obese individuals during and after submaximal treadmill exercise are the subjects of great interest to public health. After graded exercise, delayed heart rate recovery (HRR), exaggerated blood pressure (BP) response, and prolongation of QT interval are the powerful predictors of cardiovascular morbidity and mortality that may facilitate timely identification of individuals at risk of CVD and help to evaluate the effectiveness of treatment interventions. To compare the cardiovascular parameters on submaximal treadmill exercise in obese and nonobese adults. This study was conducted on 80 subjects, 40 obese (cases) and 40 normal-weight individuals (controls), belonging to the age group of 18-60 years. Each participant was subjected to submaximal treadmill exercise according to the Bruce protocol. Heart rate (HR), systolic BP and diastolic BP (SBP and DBP), mean arterial pressure (MAP), QT and corrected QT (QTc) intervals, and rate pressure product (RPP) were measured preexercise, immediately after exercise, and during passive recovery at 1 min and 5 min after exercise. The Chi-square test and Mann-Whitney U-test, whichever is appropriate, were employed for the comparison of variables between the two study groups. P < 0.05 was considered statistically significant. Mean HR immediately after exercise, at 1 min and 5 min postexercise was significantly higher in obese when compared to nonobese participants (P = 0.006, P = 0.001, P = 0.001) despite similar resting HR in both the groups (P = 0.874). Mean SBP, DBP, MAP, and RPP were significantly higher in obese in comparison to nonobese subjects in all stages, i.e. before exercise, immediately after exercise, at 1 min and 5 min after exercise. QT and QTc intervals were also found to be significantly greater in obese than nonobese subjects in all stages (P = 0.001 each). Obese subjects had higher resting BP (SBP, DBP, and MAP), QT/QTc interval, RPP, and increased response to submaximal treadmill exercise activity. Delayed HRR after exercise was also noted in obese subjects which indicates that obese populations are at risk of developing CVDs due to alteration in autonomic functions with sympathetic hyperactivity.

P446 INDEPENDENT EFFECTS OF TYPE 2 DIABETES AND OBESITY ON CARDIOPULMONARY PERFORMANCE IN SUBJECTS AT HIGH CARDIOVASCULAR RISK

Abstract Background Both obesity and type 2 diabetes (T2D) are associated with effort intolerance and heart failure. Since the two conditions often coexist and overlap, their distinct effect on cardiopulmonary performance remains to be elucidated. Methods Patients at high cardiovascular risk, free from any clinical or instrumental evidence of heart disease, with a wide range of body mass index (BMI) values, and with or without T2D underwent combined echocardiography–cardiopulmonary exercise test (eCPET). Patients were divided in T2D and controls, as well as in lean (BMI &amp;lt;25 kg/m2), overweight (BMI 25 – 30 kg/m2), and obese (BMI &amp;gt;30 kg/m2). Results A total of 206 patients was analyzed, divided in 109 patients with T2D and 97 controls. Increased BMI is associated with multiple cardiovascular dysfunctions including chronotropic insufficiency, subclinical systolic dysfunction (reduced global longitudinal strain, GLS), and impaired systolic reserve, achieving significantly lower oxygen uptake and workload. Obesity is associated with reduced lung volumes and mild ventilatory alterations at peak exercise, irrespective of diabetes. T2D patients showed more frequent LV concentric remodeling, worse systolic and diastolic performance at rest with diminished ameliorations during exercise, and worse sympatho–vagal balance as expressed by the higher prevalence of chronotropic insufficiency and delayed heart rate recovery. Nonetheless, when divided in BMI subclasses, the differences between T2D and controls were only evident among lean subjects. In fact, while no difference between T2D and controls was evident among overweight and obese patients, lean individuals with T2D display worse cardiopulmonary performance than lean controls, achieving lower workload and lower VO2peak, revealing systolic dysfunction (lower GLS) and higher LV filling pressures (E/e’). Unlike glycated hemoglobin, strong linear relationships were proven between fat mass and oxygen uptake, workload, systolic, and diastolic indices. Conclusions T2D affects LV dimensions and geometry, systo–diastolic functions, autonomic balance, cardiopulmonary capacity, and exercise tolerance, independently of the presence of obesity. Nonetheless, increased BMI is an even more powerful independent negative determinant of systolic function, autonomic balance, and effort tolerance. These early alterations might partly explain the increased risk of developing heart failure associated with diabetes and obesity.

Effect of Exercise on ECG Components and their Correlation with Body Mass Index among Young Asymptomatic Obese and Non-obese Individuals: A Cross-sectional Study

Introduction: The worldwide higher prevalence of obesity is currently one of the most important reasons for the occurrence of several health disorders, along with an increased risk of mortality and morbidity. However, the magnitude of the effect of sub-maximal aerobic exercise on cardiac autonomic and electrical function among Indian obese individuals has yet to be established. Aim: To evaluate the effect of exercise on ECG components and their correlation with Body Mass Index (BMI) among young asymptomatic obese and non-obese individuals, in order to assess the risk for developing Cardiovascular Diseases (CVD) in the future. Materials and Methods: An observational cross-sectional study was conducted at the Autonomic Research Laboratory of the Physiology Department at RG Kar Medical College and Hospital, Kolkata, between January 2017 to December 2017. Two hundred healthy medicos were divided into two groups: Obese (BMI ≥25 kg/m²; n=88) and non-obese (BMI ≥18.5 to ≤23 kg/m²; n=112). Resting Blood Pressure (BP) was manually recorded, followed by the recording of long lead-II ECG in the supine posture both at rest and ten minutes after submaximal (50% VO2 max) aerobic exercise on a treadmill using the modified Bruce protocol and following the Astrand-Rhyming nomogram. The HR, QT interval, and RR interval were recorded from the lead-II ECG. The measured QT interval was corrected using Bazett’s formula (QTC=QT/√RR). The results were analysed using both unpaired and paired t-tests and the Pearson correlation coefficient in Graphpad-Quickcalc software. Results: Significant prolongation of the QTc interval both at rest (p-value: 0.019) and after exercise (p-value: 0.044), along with delayed Heart Rate Recovery (HRR) (p-value: 0.001), were observed among the obese compared to the non-obese population. Additionally, a significantly positive linear correlation was observed between BMI and ECG components at rest (BMIRHR: r:+0.293; p: 0.005 and BMI-QTc Interval: r:+0.226; p-value: 0.034) and during the recovery state (BMI-HRR: r:+0.42; p-value: 0.00004 and BMI-QTc Interval: r:+0.365; p-value: 0.0004), only among the obese. Conclusion: At rest, obese individuals had an elevated QTc, which could be due to alterations in cardiac autonomic function, along with a significant positive correlation between BMI and RHR, indicating lower aerobic fitness in this population. Prolongation of the QTc interval, delayed decrease in HR, and a significant positive correlation with BMI after exercise in obese individuals indicated myocardial repolarisation instability, autonomic dysfunction, and an increased risk of out-of-hospital sudden cardiac events in these individuals.

Comprehensive Study of Heart Rate Recovery and Altered Ventilatory Response to Exercise in Patients with Obstructive Sleep Apnea

Abstract Background Obstructive sleep apnea (OSA) is a chronic disorder that results in many cardiovascular disorders including hypertension, arrhythmias and congestive heart failure (CHF). Polysomnography is the gold standard for diagnosis of OSA, even though up to 93% of women and 82% of men with moderate to severe OSA still remain undiagnosed. Cardiopulmonary exercise testing (CPXT) has been conventionally used for evaluation of coronary artery diseases and rehabilitation of cardiac patients. Modern systems allow for the analysis of gas exchange at rest, during exercise, and during recovery and also yield measures of oxygen uptake (V O2), carbon dioxide output (V CO2), and minute ventilation (V E) together with heart rate, blood pressure, electrocardiography findings, and symptoms. This may have clinical utility if added to the available screening tools used to identify OSA. Aim of study To assess altered ventilatory response and heart rate recovery in response to exercise in patients with obstructive sleep apnea and their relation to its severity. Methods and Results Case control study was enrolled including 30 patients with obstructive sleep apnea (OSA) divided according to severity (5 mild, 8 moderate and 17 severe) and 15 control healthy overweight with sedentary lifestyle individuals. The two groups underwent cardiopulmonary exercise testing and different pulmonary and cardiac parameters were calculated. Greater VE, VE/VCO2, VE/VO2 ratios and VE/VCO2 slope were statistically significant regarding the patients group (P &amp;lt; 0.001, F = 69.053, 104.381, 140.806 and 68.010 respectively according to ANOVA test). OSA patients had a reduced maximal exercise capacity expressed as lower VO2 peak, decreased breathing reserve (BR) and VO2 at anaerobic threshold compared to control group (P &amp;lt; 0.001, F = 22.597, 68.773 and 82.90 respectively). Delayed heart rate recovery (HRR) and weaker chronotropic response (CR) in patients with OSA than in controls with negative relationship to severity of OSA were proved (p &amp;lt; 0.001, F = 119.493 and 91.271 respectively). The study revealed elevated maximal systolic BP (max SBP), diastolic BP (max DBP) and recovery SBP in the following 2 minutes after exercise in patients with OSA relative to their healthy controls with positive relationship to the severity of OSA (P &amp;lt; 0.001, F = 37.129, 169.275 and 244.609 respectively). Conclusion Patients with OSA demonstrated exaggerated ventilatory response to exercise and autonomic dysfunction reflected by measurement of heart rate variability and reduced maximal exercise capacity than healthy controls. Abbreviations OSA, CHF, CPXT, VO2, VCO2, VE, VE/VCO2, VE/VO2, VE/VCO2, BR, CR, HRR, max SBP and max DBP.

Delayed heart rate recovery after exercise predicts development of metabolic syndrome: A retrospective cohort study.

ABSTRACTAims/IntroductionSeveral cross‐sectional studies have shown that delayed heart rate recovery (HRR) after exercise is associated with the development of metabolic syndrome (MetS). However, there has been a lack of comprehensively designed longitudinal studies. Therefore, our aim was to evaluate the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with incident MetS.Materials and MethodsThis was a retrospective longitudinal cohort study of participants without MetS, diabetes, or cardiovascular diseases. The HRR was calculated as the peak heart rate minus the resting heart rate after a 1 min rest (HRR1), a 2 min rest (HRR2), and a 3 min rest (HRR3). Multivariate Cox proportional hazards analysis was performed to investigate the association between HRR and development of MetS.ResultsThere were 676 (31.2%) incident cases of MetS identified during the follow‐up period (9,683 person‐years). The only statistically significant relationship was between HRR3 and the development of MetS. The hazard ratios (HRs) (95% confidence interval [CI]) of incident MetS comparing the first and second tertiles to the third tertile of HRR3 were 1.492 (1.146–1.943) and 1.277 (1.004–1.624) with P = 0.003 after adjustment for multiple risk factors. As a continuous variable, the HR (95% CI) of incident MetS associated with each one‐beat decrease in HRR3 was 1.015 (1.005–1.026) with P = 0.004 after full adjustments. An HRR3 value ≤45 beats per minute (bpm) was associated with a higher risk of incident MetS compared with values >45 bpm, with an HR (95% CI) of 1.304 (1.061–1.602) and P = 0.001.ConclusionsThe slow phase of HRR, particularly HRR3, might be more sensitive at predicting the risk of MetS.

Heart rate recovery in asthmatic children and adolescents after clinical field test

BackgroundInflammation caused by chronic lung disease in childhood may lead to delayed heart rate recovery (HRR) however, there is lack of evidence on HRR in this population. The aim was to assess HRR after functional capacity testing in asthmatic children and adolescents and to compare with severity and disease control.MethodThis was a study secondary to a randomized control trial. The modified shuttle test (MST) was performed to assess functional capacity and HRR. This is an externally cadenced test in which the distance walked is the outcome. HRR was assessed after MST and was defined as HR at exercise peak minus HR in the second minute after the end of exercise. Asthma control was assessed by the Asthma Control Test (ACT). Data normality was tested by Shapiro Wilk and the comparison between groups was made by Student’s t test or Mann Whitney test for numerical variables, and by Chi-square test for categorical variables. Statistical significance was considered when p < 0.05. SPSS version 20 was used in the analyzes.ResultsThe sample included 77 patients diagnosed with asthma (asthma group - AG) who were regularly treated for asthma. Control group (CG) consisted of 44 volunteers considered healthy, matched in age and gender to AG. The median age of CG was 12 (10–14) years and in AG 11 (9–13 years) being classified as mild to moderate asthmatic, and 57% of the sample had controlled asthma by ACT. Distance walked in the CG was 952 ± 286 m and AG 799 ± 313 m, p = 0.001. HRR was more efficient in CG (79 ± 15 bpm) compared to AG (69 ± 12 bpm), p = 0.001. The mild (69 ± 12 beats) and severe (72 ± 15 beats) AG presented worse HRR compared to control group (79 ± 15 bpm), p < 0.05.ConclusionsAsthmatic children and adolescents have delayed HRR after modified Shuttle test compared to their peers, suggesting that asthma leads to autonomic nervous system imbalance.Trial registration: Registered in Clinical Trials under number NCT02383069 and approved by the Universidade Nove de Julho - UNINOVE Research Ethics Committee, protocol number 738192/2014.

The impact of delayed heart rate recovery on prevalent hypertension

ABSTRACT Objectives: Delayed heart rate recovery (HRR) is considered an indicator of autonomic nervous dysfunction, which is a primary pathological mechanism of hypertension. The present study aimed to explore the independent association between delayed HRR and prevalent hypertension. Methods: In this cross-sectional study, 314 inpatients were recruited between January 2018 and December 2019. HRR was defined as the peak heart rate during exercise minus the 2nd-minute heart rate after exercise in the treadmill exercise test. Results: The mean HRR in the hypertension group was lower than that in the non-hypertension group (41 bpm vs. 46 bpm; P < 0.001). After full adjustment, each standard deviation increase in HRR was associated with a 35% decrease in the risk of prevalent hypertension (OR: 0.65, 95% CI: 0.48–0.87; P = 0.004). When the HRR was divided into quartiles, the risk in the top quartile was 26% of that in the bottom quartile (OR: 0.26, 95% CI: 0.12–0.56; P = 0.001). Furthermore, smooth curve fitting showed that the risk of prevalent hypertension decreased linearly with the increase in HRR. Conclusion: Delayed HRR was independently associated with prevalent hypertension. The association was linear and robust over the entire range of HRR. The present study suggested that delayed HRR could be used to optimize hypertension risk stratification.

Heart rate recovery after exercise as a prognostic predictor in patients with atrial fibrillation

Abstract Background A delayed heart rate recovery (HRR) after exercise is related to mortality in sinus rhythm. This study aimed to investigate this concept can be applied to patients with atrial fibrillation (AF). Methods We analyzed 483 patients with AF (mean 65 years, male 74%). HRR integral was calculated by integrating the difference in HR in every 3 second between the end of exercise and the specified time after the exercise (30, 60, 120 and 180 seconds). After evaluating the prognostic power of each HRR integral, we selected HRR integral of 180 seconds (180HRR-integral). Results We divided the patients into two groups using median value of 180HRR-integral. All-cause mortality, the incidence of cardiovascular events and heart failure events were higher in the poor 180HRR-integral. After adjustment for covariates, the impact of the high 180HRR-integral for all-cause mortality was 3.15 (p=0.057), 1.77 for cardiovascular events (p=0.067) and 1.28 for heart failure events (p=0.519). Conclusion Poor HRR was associated with worse prognosis in patients with AF. Funding Acknowledgement Type of funding source: None

P11 deficiency increases stress reactivity along with HPA axis and autonomic hyperresponsiveness

Patients suffering from mood disorders and anxiety commonly exhibit hypothalamic–pituitary–adrenocortical (HPA) axis and autonomic hyperresponsiveness. A wealth of data using preclinical animal models and human patient samples indicate that p11 deficiency is implicated in depression-like phenotypes. In the present study, we used p11-deficient (p11KO) mice to study potential roles of p11 in stress responsiveness. We measured stress response using behavioral, endocrine, and physiological readouts across early postnatal and adult life. Our data show that p11KO pups respond more strongly to maternal separation than wild-type pups, even though their mothers show no deficits in maternal behavior. Adult p11KO mice display hyperactivity of the HPA axis, which is paralleled by depression- and anxiety-like behaviors. p11 was found to be highly enriched in vasopressinergic cells of the paraventricular nucleus and regulates HPA hyperactivity in a V1B receptor-dependent manner. Moreover, p11KO mice display sympathetic–adrenal–medullary (SAM) axis hyperactivity, with elevated adrenal norepinephrine and epinephrine levels. Using conditional p11KO mice, we demonstrate that this SAM hyperactivity is partially regulated by the loss of p11 in serotonergic neurons of the raphe nuclei. Telemetric electrocardiogram measurements show delayed heart rate recovery in p11KO mice in response to novelty exposure and during expression of fear following auditory trace fear conditioning. Furthermore, p11KO mice have elevated basal heart rate in fear conditioning tests indicating increased autonomic responsiveness. This set of experiments provide strong and versatile evidence that p11 deficiency leads to HPA and SAM axes hyperresponsiveness along with increased stress reactivity.

Chronotropic Index And Heart Rate Recovery After Exercise In Adolescentes With Down Syndrome

Individuals with Down syndrome (DS) have a reduced heart rate (HR) response to exercise which is the main contributor to low cardiorespiratory fitness in this population. A previous study has shown delayed heart rate recovery (HHR) in adults with DS performing exercise testing, however there is still a gap regarding the HRR response and chronotropic index in adolescents with DS. PURPOSE: To evaluate heart rate reponse treadmill exercise test and its impact on exercise in adolescents with DS compared to non-DS. METHODS: Eleven adolescents with DS (7 girls, 4 boys; age 14.1 ± 1.04 years) and 10 non-DS (6 girls, 4 boys; age 13.7 ± 1.2 years) performed peak treadmill test with heart rate measurements. HRR was defined as the reduction in heart rate from the rate at peak exercise to the rate at 1 and 2 minutes after the cessation of exercise. Chronotropic index was calculated by a formula [(peak HR – resting HR) / (220–age – resting HR)] *100. For comparisons between groups, the independent t test was used. RESULTS: Compared to control group, adolescents with DS presented lower peak HR, loading time (s) and distance (m) (p < 0.05). In contrast, adolescents with DS had resting HR values similar to those non-DS. Participants with DS showed slower HRR than non-DS at 1 minute (DS: 21.1 ± 6.95 beats / min; controls: 47.1 ± 6.99 beats / min) and 2 minutes (DS: 28.5 ± 7.38 beats / min; controls: 49.4 ± 6.39 beats / min) of recovery (p <0,05). In addition, adolescents with DS have a lower CI (0.84 ± 0.09 vs 0.66 ± 0.09, p = 0.0001) when compared to their peers. CONCLUSION: Adolescents with DS had attenuated post-exercise HRR that may be related to lower chronotropic response at peak intensities.

1526-P: Delayed Heart Rate Recovery after Exercise as a Risk Factor of Incident Metabolic Syndrome: A Retrospective Cohort Study

Background: There have been several cross-sectional studies reporting that delayed heart rate recovery (HRR) after exercise is associated with the development of the metabolic syndrome (MetS). However, there have been few longitudinal studies. We evaluated the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the incident MetS including metabolic parameters as adjusting factors. Methods: A retrospective longitudinal cohort study of participants without MetS, diabetes or cardiovascular diseases has been designed. HRR was calculated as peak heart rate minus heart rate after a 1-minute rest (HRR 1), heart rate after a 2-minute rest (HRR 2), and heart rate after a 3-minute rest (HRR 3). To investigate the association between HRR and incident MetS, multivariate Cox proportional hazards analysis was performed. Results: During 9,683 person-years of follow-up between 2006 and 2012, there were 676 (31.2%) incident cases of the MetS. After adjustment for age, sex, smoking status, baseline heart rate, peak heart rate, peak oxygen uptake, hs-CRP, waist circumference, systolic blood pressure, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, and HbA1c, the hazard ratios (HR) [95% confidence interval (CI)] of incident MetS comparing the first and second tertiles to the third tertile of HRR 3 were 1.492 (1.146-1.943) and 1.277 (1.004-1.624) (P for trend = 0.003). As a continuous variable, after full adjustments, the HR (95% CI) of incident MetS associated with each 1-second decrease in HRR3 was 1.015 (1.005 -1.026) (P = 0.004). Conclusion: Delayed HRR 3 after exercise could predict incident MetS, even after adjusting for metabolic parameters. However, HRR 1 and HRR 2 have not shown the statistic significance. Disclosure T. Yu: None. S. Jin: None. K. Hur: None. J. Bae: None. J. Jee: None. J. Kim: None. M. Lee: None.

Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats.

Metabolic syndrome (MetS) has become a global epidemic. MetS is a serious health problem because of its related cardiovascular complications, which include hypertension and delayed heart rate recovery after exercise. The molecular bases of cardiac dysfunction in MetS are still under scrutiny and may be related to anomalies in the activity and expression of key proteins involved in the cardiac excitation–contraction coupling (ECC). The cardiac Ca2+ channel/ryanodine receptor (RyR2) participates in releasing Ca2+ from internal stores and plays a key role in the modulation of ECC. We examined alterations in expression, phosphorylation status, Ca2+ sensitivity, and in situ function (by measuring Ca2+ sparks and Ca2+ transients) of RyR2; alterations in these characteristics could help to explain the Ca2+ handling disturbances in MetS cardiomyocytes. MetS was induced in rats by adding commercially refined sugar (30% sucrose) to their drinking water for 24 weeks. Cardiomyocytes of MetS rats displayed decreased Ca2+ transient amplitude and cell contractility at all stimulation frequencies. Quiescent MetS cardiomyocytes showed a decrease in Ca2+ spark frequency, amplitude, and spark-mediated Ca2+ leak. The [3H]-ryanodine binding data showed that functionally active RyRs are significantly diminished in MetS heart microsomes; and exhibited rapid Ca2+-induced inactivation. The phosphorylation of corresponding Ser2814 (a preferential target for CaMKII) of the hRyR2 was significantly diminished. RyR2 protein expression and Ser2808 phosphorylation level were both unchanged. Further, we demonstrated that cardiomyocyte Ca2+ mishandling was associated with reduced SERCA pump activity due to decreased Thr17-PLN phosphorylation, suggesting a downregulation of CaMKII in MetS hearts, though the SR Ca2+ load remained unchanged. The reduction in the phosphorylation level of RyR2 at Ser2814 decreases RyR2 availability for activation during ECC. In conclusion, the impaired in situ activity of RyR2 may also account for the poor overall cardiac outcome reported in MetS patients; hence, the SERCA pump and RyR2 are both attractive potential targets for future therapies.

Cardiac function in adolescents with obesity: cardiometabolic risk factors and impact on physical fitness.

To gain greater insights in the etiology and clinical consequences of altered cardiac function in obese adolescents. Therefore,we aimed to examine cardiac structure and function in obese adolescents, and to examine associations between altered cardiac function/structure and cardiometabolic disease risk factors or cardiopulmonary exercise capacity. In 29 obese (BMI 31.6 ± 4.2 kg/m², age 13.4 ± 1.1 years) and 29 lean (BMI 19.5 ± 2.4 kg/m², age 14.0 ± 1.5 years) adolescents, fasted blood samples were collected to study hematology, biochemistry, liver function, glycemic control, lipid profile, and hormones, followed by a transthoracic echocardiography to assess cardiac structure/function, and a cardiopulmonary exercise test (CPET) to assess cardiopulmonary exercise parameters. Regression analyses were applied to examine relations between altered echocardiographic parameters and blood parameters or CPET parameters in the entire group. In obese adolescents, left ventricular septum thickness, left atrial diameter, mitral A-wave velocity, E/e' ratio were significantly elevated (p < 0.05), as opposed to lean controls, while mitral e'-wave velocity was significantly lowered (p < 0.01). Elevated homeostatic model assessment of insulin resistance and blood insulin, c-reactive protein, and uric acid concentrations (all significantly elevated in obese adolescents) were independent risk factors for an altered cardiac diastolic function (p < 0.01). An altered cardiac diastolic function was not related to exercise tolerance but to a delayed heart rate recovery (HRR; p < 0.01). In obese adolescents, an altered cardiac diastolic function was independently related to hyperinsulinemia and whole-body insulin resistance, and only revealed by a delayed HRR during CPET. This indicates that both hyperinsulinemia, whole-body insulin resistance, and delayed HRR could be regarded as clinically relevant outcome parameters.

Relation of Exercise Heart Rate Recovery to Predict Cardiometabolic Syndrome in Men

We examined the hypothesis that delayed heart rate recovery (HRR) after exercise testing, an estimate of decreased autonomic function, predicts the risk of cardiometabolic syndrome (MetS) and is associated with continuous MetS risk scores in healthy men. Participants were 2,740 men who underwent general health examinations and had no evidence of MetS, cardiovascular diseases, diabetes, and hypertension at baseline. Baseline HRR was calculated as the difference between peak heart rate attained during exercise testing and the heart rate at 1 (HRR 1) and 2 minutes (HRR 2) after test termination. Incident MetS was defined as participants having ≥3 MetS components, and continuous MetS risk score was computed as the sum of z-score of 5 risk factors at follow-up. The incidence of MetS was 61/1,000 person-years during an average follow-up of 5 years. The relative risks and 95% confidence interval (CI) of incident MetS in the lowest quartiles of HRR 1 and HRR 2 versus the highest quartile were 1.24 (95% CI 1.02 to 1.51) and 2.02 (95% CI 1.58 to 2.60), respectively, after adjusting for potential confounders, including peak oxygen uptake and resting heart rate. HRR 1 (ß = -0.052, p = 0.005) and HRR 2 (ß = -0.058, p = 0.009) were independently associated with clustered MetS risk scores after adjusting for covariates. In conclusion, the independent association between delayed HRR after exercise testing and incident MetS and continuous MetS risk scores suggests that decreased autonomic function may be considered as a parameter to predict the future likelihood of MetS.

Heart Rate Recovery, Physical Activity Level, and Functional Status in Subjects With COPD.

A normal heart rate reflects the balance between the sympathetic and parasympathetic autonomic nervous system. When the difference between heart rate at the end of an exercise test and after 1 min of recovery, known as the 1-min heart rate recovery, is ≤ 12 beats/min, this may indicate an abnormal delay. We sought to compare physical activity patterns and subjects' functional status with COPD with or without delayed 1-min heart rate recovery after the 6-min walk test (6MWT). 145 subjects with COPD (78 men, median [interquartile range (IQR)] age 65 [60-73] y, body mass index 25 [21-30] kg/m2, FEV1 45 ± 15% predicted) were underwent the following assessments: spirometry, 6MWT, functional status, and physical activity in daily life (PADL). A delayed heart rate recovery of 1 min was defined as ≤ 12 beats/min. Subjects with delayed 1-min heart rate recovery walked a shorter distance in the 6MWT compared to subjects without delayed heart rate recovery (median [IQR] 435 [390-507] m vs 477 [425-515] m, P = .01; 81 [71-87] vs 87 [79-98]% predicted, P = .002). Regarding PADL, subjects with delayed heart rate recovery spent less time in the standing position (mean ± SD 185 ± 89 min vs 250 ± 107 min, P = .002) and more time in sedentary positions (472 ± 110 min vs 394 ± 129 min, P = .002). Scores based on the self-care domain of the London Chest Activity of Daily Living questionnaire and the activity domain of the Pulmonary Functional Status and Dyspnea questionnaire were also worse in the group with delayed heart rate recovery (6 ± 2 points vs 5 ± 2 points; P = .039 and 29 ± 24 points vs 19 ± 17 points; P = .037, respectively). Individuals with COPD who exhibit delayed 1-min heart rate recovery after the 6MWT exhibited worse exercise capacity as well as a more pronounced sedentary lifestyle and worse functional status than those without delayed heart rate recovery. Despite its assessment simplicity, heart rate recovery after the 6MWT can be further explored as a promising outcome in COPD.

Abstract P545: Prehypertension is Associated With Metabolic Disturbance and Delayed Heart Rate Recovery: Potential Link Between Prehypertension and Metabolic-autonomic Dysfunction

Background: Prehypertension is a highly prevalent condition, but its pathophysiology is still poorly understood. Heart rate recovery (HRR), noninvasive parameter acquired during treadmill test, is an index of autonomic dysfunction. We aimed to evaluate the association of prehypertension with autonomic dysfunction, and further, to identify the determinants of autonomic dysfunction. Methods: We retrospectively identified 557 asymptomatic participants who did not have hypertension and underwent comprehensive health check-ups including cardiopulmonary exercise test. They were categorized into two groups: optimal blood pressure (BP) (systolic BP&lt;120mmHg and diastolic BP&lt;80mmHg, n=277) and prehypertension (120≤systolic BP&lt;140mmHg and/or 80 ≤diastolic BP&lt;89mmHg, n=280). HRR at 1 minute (HRR 1 ) was also calculated as follows: peak heart rate (HR) minus HR after 1-minute recovery. Results: Prehypertension group exhibited more obese feature (waist circumference, 83.3±7.3 vs. 87.4±8.1cm; p&lt;0.001) and metabolic disturbance (HOMA-IR, 0.93±0.85 vs. 1.26±1.06; uric acid 5.5±1.4 vs. 5.9±1.4; HDL-cholesterol 52.4±13.6 vs. 48.5±12.2 mg/dL; all p&lt;0.005). They also had high pulse wave velocity (PWV, 1315.7±143.0 vs. 1453.1±187.1cm/sec, p&lt;0.001). Although the resting HR and peak exercise HR did not differ between the groups, prehypertension group exhibited a significantly lower HRR 1 level, suggesting an impaired parasympathetic reactivation in the prehypertension (39.3±14.7 vs. 36.2±14.9 beats/min, p=0.016). In a multivariate linear regression analysis, resting HR ( ß =-0.360, p&lt;0.001), waist circumference ( ß =-0.195, p=0.018), PWV ( ß =-0.008, p=0.017), and HDL-cholesterol ( ß =0.105, p=0.036) were independent determinants of the HRR 1 . Conclusions: Prehypertension is associated with metabolic disturbance and autonomic dysfunction. HRR is mainly determined by waist circumference, arterial stiffness, and dyslipidemia even after adjustment for the resting HR. Our observation suggests the possible role of metabolic-autonomic abnormality in the pathogenesis of prehypertension.

Autonomic regulation of systemic inflammation in humans: A multi-center, blinded observational cohort study

ObjectiveExperimental animal models demonstrate that autonomic activity regulates systemic inflammation. By contrast, human studies are limited in number and exclusively use heart rate variability (HRV) as an index of cardiac autonomic regulation. HRV measures are primarily dependent on, and need to be corrected for, heart rate. Thus, independent autonomic measures are required to confirm HRV-based findings. Here, the authors sought to replicate the findings of preceding HRV-based studies by using HRV-independent, exercise-evoked sympathetic and parasympathetic measures of cardiac autonomic regulation to examine the relationship between autonomic function and systemic inflammation. MethodsSympathetic function was assessed by measuring heart rate changes during unloaded pedaling prior to onset of exercise, divided into quartiles; an anticipatory heart rate (AHRR) rise during this period is evoked by mental stress in many individuals. Parasympathetic function was assessed by heart rate recovery (HRR) 60s after finishing cardiopulmonary exercise testing, divided into quartiles. Parasympathetic dysfunction was defined by delayed heart rate recovery (HRR) ≤12.beats.min−1, a threshold value associated with higher cardiovascular morbidity/mortality in the general population. Systemic inflammation was primarily assessed by neutrophil-lymphocyte ratio (NLR), where a ratio >4 is prognostic across several inflammatory diseases and correlates strongly with elevated plasma levels of pro-inflammatory cytokines. High-sensitivity C-reactive protein (hsCRP) was also measured. ResultsIn 1624 subjects (65±14y; 67.9% male), lower HRR (impaired vagal activity) was associated with progressively higher NLR (p=0.004 for trend across quartiles). Delayed HRR, recorded in 646/1624 (39.6%) subjects, was associated with neutrophil-lymphocyte ratio >4 (relative risk: 1.43 (95%CI: 1.18–1.74); P=0.0003). Similar results were found for hsCRP (p=0.045). By contrast, AHRR was not associated with NLR (relative risk: 1.24 (95%CI: 0.94–1.65); P=0.14). ConclusionsDelayed HRR, a robust measure of parasympathetic dysfunction, is independently associated with leukocyte ratios indicative of systemic inflammation. These results further support a role for parasympathetic modulation of systemic inflammation in humans.